Is azithromycin (Zithromax) safe to use during pregnancy?

Azithromycin Safety in Pregnancy

Azithromycin is generally safe to use during pregnancy when clinically indicated and benefits outweigh potential risks. 1 The drug should be used for specific indications where its efficacy has been established and alternative treatments may pose greater risks.

Safety Profile

• Azithromycin is classified as FDA Pregnancy Category B, indicating that animal reproduction studies have shown no evidence of harm to the fetus, though adequate and well-controlled studies in pregnant women are lacking 2
• The Centers for Disease Control and Prevention (CDC) specifically recommends azithromycin for several conditions during pregnancy, including:
  • First-line treatment for chlamydial infections
  • Prophylaxis for Mycobacterium avium complex in HIV-infected pregnant women 1

Clinical Evidence Supporting Safety

• According to North American clinical practice guidelines, azithromycin is considered safe in pregnancy with no adverse effects reported 3
• Unlike some other antibiotics, azithromycin does not require dose adjustment during pregnancy as it does not affect the cytochrome P450 system, making it safer to use with other medications 1
• Reproductive studies in rats and mice at doses up to 4 and 2 times the human daily dose (based on mg/m²) showed no evidence of harm to the fetus 2

Potential Concerns

• Some studies have reported conflicting results regarding fetal and neonatal outcomes following prenatal azithromycin exposure 4
• Concerns have been raised about potential risks including:
  • Spontaneous miscarriage
  • Major congenital malformations
  • Cardiovascular malformations
  • Preterm birth
  • Low birth weight 4

However, there is no conclusive evidence supporting these concerns, and the most recent guidelines continue to support azithromycin use when indicated 3, 1.

Specific Clinical Applications

• Azithromycin is recommended as first-line treatment for chlamydial infections in pregnancy with a single 1g oral dose 1
• It has been studied as part of intermittent preventive treatment in pregnancy (IPTp) for malaria, showing reduced risk of low birth weight and prematurity 5
• Recent research demonstrates that a single 2g oral dose of azithromycin during labor significantly reduced the risk of maternal sepsis without increasing adverse events 6

Monitoring and Precautions

• Avoid co-administration with medications that prolong QT interval due to risk of cardiac arrhythmias 1
• Monitor for common side effects, including liver enzyme abnormalities and hearing impairment, especially when used with other medications like nelfinavir 2
• Elderly patients may be more susceptible to torsades de pointes arrhythmia, though this is less relevant to the pregnant population 2

Conclusion for Clinical Practice

When prescribing azithromycin during pregnancy:

1. Use only when clinically indicated for specific infections
2. Prefer azithromycin over other antibiotics with established teratogenicity (e.g., doxycycline, fluoroquinolones)
3. Use standard recommended dosages without adjustment for pregnancy
4. Monitor for common side effects
5. Avoid co-administration with QT-prolonging medications

For women with chronic conditions requiring long-term azithromycin (e.g., cystic fibrosis), the benefits of continuing treatment during pregnancy typically outweigh the potential risks of discontinuation 7.